Article comprising natural polymer-based patch product and corresponding production method

Abstract

The present invention relates to an article comprising a patch product disposed on a base carrier, the patch product comprising a membrane matrix capable of being absorbed by the skin, the membrane matrix being formed from at least one electrospun fiber consisting of a first compound to be electrospun and an electrospinning promoter.

Description

Technical Field

[0001] The present invention relates to an article comprising a product. More particularly, the present invention relates to a patch product capable of being absorbed by the skin and based on a biocompatible polymer compound, the product consisting of fibers, in particular nanofibers, preferably obtained by electrospinning, deposited on a carrier and packaged. Although not absorbable by the skin, the carrier is also based on a biocompatible polymer compound. Background Art

[0002] Products for direct application to the skin are well known and are formulated in various forms compatible with and / or absorbed by the skin, such as emulsions, creams, lotions, serums, gels, powders, oils, sunscreens, etc., or other formulations.

[0003] However, these products can sometimes be laborious to apply on the skin, sometimes require extended application time or extended massaging to fully absorb into the dermis, and sometimes leave residue on the fingers or hands or on any applicator used.

[0004] There are also products, in particular cosmetics, which are applied by means of a physical carrier, usually a cellulosic carrier, which facilitates their application to the skin, such as, in particular, make-up removing wipes soaked in special detergent compositions.

[0005] A disadvantage of this type of product is that it is necessary to dispose of the physical fiber carrier and packaging after use, the former having no other function except that of a carrier.

[0006] Furthermore, known fibrous physical carriers have a specific surface and are not able to properly transport and release active ingredients.

[0007] The problem is also that, in general, cosmetic compositions for use on the skin, for example those to be applied, such as creams, or pastes in general, provide for the use of compounds that have a function on the skin and compounds that have a unique function on the structure of the formulation.

[0008] Skin-functional compounds are partially or completely absorbed by the skin and benefit the treated body part. Usually, such compounds represent so-called active ingredients.

[0009] The compounds that contribute unique functionality to the formulation structure help to obtain the composition to be applied, whether it is an emulsion, slurry or fluid, oil stone, water or gel.

[0010] The effect of the compound having a unique function on the formulation structure may affect the way the composition is stored, or the consistency of the composition before and / or during use, and therefore its consistency when applied to the skin to be treated.

[0011] For example, a compound with a unique function to the formulation structure can make the composition soft, fluid or viscous; it can obtain a gel, or prevent the separation between oily and aqueous compounds in an emulsion. In addition, a compound with a unique function allows the preservation of the composition, especially in the presence of water.

[0012] The problem that arises is that many of the compounds used, due to their function on the structure of the formulation, do not bring any benefit to the skin and in fact they may even lead to further deterioration of the treated skin. In fact, a part of the compounds that have a unique function on the structure of the formulation have no effect on the skin or may cause, for example, further drying, closure of pores, or the development of allergies, dermatitis, etc.

[0013] Among the compounds with a unique function for the formulation structure, one can identify, for example, silicones, petroleum products (e.g. paraffin), alcohols, fragrances, stabilizers, preservatives, emulsifiers, whose main function is to give the formulation of the composition a "silky effect" consistency when in contact with the skin and / or to provide stability to the oily part, or to increase the viscosity of gel formulations and / or to increase the emollient and moisturizing effect of emulsions.

[0014] For example, such compounds having a unique function to the formulation structure cause problems such as lack of skin compatibility, preventing the skin from breathing, and even leading to, for example, gradual drying of the skin, closure of pores and / or increased sensitization.

[0015] It is also known that the presence of alcohol and preservatives allows, on the one hand, the preservation of the composition, but on the other hand they can increase the sensitization of the skin, thus triggering dermatitis, allergies or similar disorders.

[0016] A product is known from WO 2021 / 161256, which comprises a cosmetic patch product based on fibers made of a biocompatible material capable of being absorbed by the skin, which is deposited on a carrier made of a heat-sealable plastic material, in particular polybutylene succinate-adipate PBSA or polylactic acid PLA.

[0017] This type of patch product solves some of the above problems, but still does not fully meet the needs of the industry because the material used is not completely biodegradable. In addition, it has a hardness that does not allow for good application of the product, especially in certain areas of the face with uneven surfaces, such as the nose area.

[0018] Therefore, there is a need to develop a product that overcomes at least one of the shortcomings of the prior art.

[0019] In particular, it is an object of the present invention to provide a product that can be applied simply and quickly to the skin in any area of ​​the body.

[0020] Another object of the present invention is to provide a product having a biodegradable physical carrier.

[0021] Another object is to provide a product with a specific surface in order to optimize the transport and release of the active ingredient, if present.

[0022] The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages. Summary of the invention

[0023] The invention is set forth and characterized in the independent claims. The dependent claims describe other characteristics of the invention or variants to the main inventive idea.

[0024] According to the above-mentioned purpose, and solving the above-mentioned technical problems in a novel and original way, while achieving considerable advantages compared with the prior art, the product according to the present invention includes a patch product and a base carrier on which the patch product is deposited, the patch product contains a membrane matrix that can be absorbed by the skin, the membrane matrix is ​​formed by at least one electrospun fiber, and the electrospun fiber is composed of a first compound to be electrospun and an electrospinning accelerator.

[0025] According to one aspect of the invention, the base carrier comprises a biodegradable film based on polysaccharides that cannot be absorbed by the skin. Preferably, the film is made of polysaccharides, that is, the polysaccharides are the material constituting the film. Advantageously, the polysaccharides are starch.

[0026] In a particularly advantageous manner, the base carrier consists of a biodegradable film based on polysaccharides which is not absorbable by the skin.

[0027] Doing so at least achieves the advantage of having a biodegradable and decomposable substrate carrier. When applied to the skin, the polysaccharide carrier is essentially adaptable and formable, partly because its water absorption degree can change its rigidity and make it softer. This allows to improve the application of patch products in areas with many bumps (such as nose areas) on the skin, and in any case ensures that the entire surface of the film matrix adheres to the skin, increasing its absorptivity. Therefore, the substrate carrier at the substrate of the present invention is also particularly suitable for curved, convex or concave areas, such as forehead, temple, cheekbone, cheek, eye contour, etc. Another advantage is that, since the carrier is a polysaccharide, it comprises a large amount of hydroxyl-OH groups, making it suitable for moisturizing the skin. This moisturizing effect is combined with the moisturizing effect of the film matrix, and compared with the same film matrix placed on a carrier made of conventional materials, the film matrix is ​​more easily dissolved and enters the skin.

[0028] Furthermore, polysaccharide films, especially those made from starch, have good barrier properties, making them suitable for forming packaging for patch products.

[0029] According to some embodiments of the present invention, the starch is selected from corn starch, potato starch, rice starch, wheat starch, tapioca starch and mixtures thereof. Preferably, the components of this group are not genetically modified.

[0030] Preferably, the starch has a high amylose content, i.e., it has an amylose concentration greater than 50% by weight based on the weight of the starch itself, more preferably greater than 60% by weight, even more preferably greater than 70% by weight based on the weight of the starch. Since amylose has a more linear and longer structure than amylopectin, it facilitates the formation of starch-based films.

[0031] According to other embodiments of the present invention, the thickness of the polysaccharide based film is less than 1 mm, preferably less than 0.5 mm.

[0032] According to other embodiments of the present invention, the first compound to be electrospun is a polymer suitable for electrospinning and is selected from the group consisting of a first polysaccharide, collagen, gelatin, albumin, elastin and derivatives thereof. Advantageously, the first polysaccharide is selected from the group consisting of xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, starch, gelatin, β-glucan, glycosaminoglycan, mucopolysaccharide, water-soluble polysaccharide and derivatives thereof.

[0033] Preferably, the cellulose derivative is selected from hydroxypropyl methylcellulose HPMC, hydroxypropyl cellulose HPC, hydroxyethyl cellulose HEC, sodium carboxymethyl cellulose Na-CMC. Glycosaminoglycan GAG or mucopolysaccharide can be selected from chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate and hyaluronic acid HA. Water-soluble polysaccharides can be selected from galactomannan, xylan, gum arabic, gum ghatti, glucomannan, acemannan, soluble dietary fiber, glycogen, straight-chain starch and polysaccharides from plants, bacteria and fungi.

[0034] According to other embodiments of the invention, the spinning facilitator is a carrier polymer, possibly without filler, selected from a second polysaccharide chemically different from the first polysaccharide, possibly with the presence of poly(ethylene oxide) PEO. Advantageously, the carrier polymer is also biocompatible, possibly without filler.

[0035] Preferably, the electrospinning accelerator is selected from pullulan and alginate, possibly mixed with poly(ethylene oxide). The accelerator may also comprise a mixture of pullulan and alginate. More preferably, the accelerator is chemically different from the first compound to be electrospun, i.e., the first compound to be electrospun is not pullulan or alginate.

[0036] According to other embodiments of the present invention, the fiber is further composed of a surfactant.

[0037] The surfactant is advantageously a biosurfactant, ie a surfactant of biological and organic origin. In particular, the surfactant is obtained by fermentation of gram-positive microorganisms. Such surfactants have a biological origin, which makes them biocompatible.

[0038] Preferably, the surfactant is selected from lipopeptides, in particular lipopeptides obtained from Bacillus species. More preferably, the surfactant is selected from the surfactin family, in particular from surfactin, pumilacidin and lichenysin.

[0039] Advantageously, the concentration of the surfactant is from 0.1% to 5% by weight, more advantageously from 0.2% to 2% by weight, even more advantageously from 0.5% to 1% by weight, based on the total weight of the fiber.

[0040] According to some embodiments of the present invention, the electrospun fiber has a flat ribbon shape. That is, the fiber has an elliptical cross-section, rather than a circular cross-section.

[0041] According to some embodiments, the film substrate is in the form of a nonwoven fabric.

[0042] According to other embodiments, the film matrix contains one or more active ingredients selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients. Here and in this specification, the expression "active ingredient" refers to compounds that have a function on the body or a part of the body, which are partially or completely absorbed by the skin and bring benefits to the treated part of the body.

[0043] Advantageously, the one or more active ingredients are chosen from one or more peptides and their metabolites or derivatives. One class of peptides that can be used as active ingredients are tetrapeptides and their metabolites or derivatives, preferably acetyl tetrapeptides and their metabolites or derivatives. Among the acetyl tetrapeptides, we can mention for example acetyl tetrapeptide-9 and acetyl tetrapeptide-11, which are two anti-aging active compounds that act on the skin matrix to improve its structure and the elasticity and firmness of the skin, respectively.

[0044] According to some embodiments, the one or more active ingredients include a humectant such as mannitol, a pH adjuster such as sodium hydroxide, and / or an anti-wrinkle compound such as aminobutyric acid.

[0045] One advantage of the articles according to the embodiments described herein is that the patch products contained therein are completely absorbed by the skin together with the active ingredients present (e.g., cosmetic, pharmaceutical or nutritional active ingredients). In addition to complete absorption, the absorption is also rapid, and it has been demonstrated that the patch products of the articles of the present invention can be completely absorbed within only a few minutes from the time they are applied to the skin.

[0046] Another advantage is that the form in which the product is presented does not imply the need for the presence of compounds with unique functionalities to the structure, since the active ingredients are carried and delivered by the membrane matrix, and the latter is completely biocompatible and can be absorbed by the skin without causing any risk or damage to the skin itself.

[0047] Another advantage of the preparation with cosmetic, pharmaceutical or nutraceutical is that it is possible to achieve much higher local concentrations of the target compound than can be obtained with conventional preparations. In fact, even with polysaccharides, collagen, gelatin, albumin, elastin and their low molecular weight derivatives, it is not possible to achieve high concentrations because the viscosity of the product increases too much and it is not possible to exceed 5% by weight to 10% by weight. With this preparation, the cosmetic, pharmaceutical or nutraceutical allows to apply concentrations of up to 50% by weight of the target compound on the skin.

[0048] According to another aspect of the present invention, a method for producing an article comprising a patch product disposed on a substrate carrier comprises the step of electrospinning a composition comprising a first compound to be electrospun and an electrospinning accelerator to obtain electrospun fibers, wherein the electrospun fibers are directly deposited on a substrate carrier comprising a polysaccharide-based biodegradable film that is not absorbable by the skin, the film preferably being made of starch.

[0049] In a particularly advantageous manner, the base carrier consists of a biodegradable film based on polysaccharides which is not absorbable by the skin.

[0050] According to some embodiments of the present invention, the starch is selected from corn starch, potato starch, rice starch, wheat starch, tapioca starch and mixtures thereof. Preferably, the components of this group are not genetically modified.

[0051] Preferably, the starch has a high amylose content, i.e., it has an amylose concentration greater than 50% by weight based on the weight of the starch itself, more preferably greater than 60% by weight, even more preferably greater than 70% by weight based on the weight of the starch. Since amylose has a more linear and longer structure than amylopectin, it facilitates the formation of starch-based films.

[0052] According to other embodiments of the present invention, the thickness of the polysaccharide based film is less than 1 mm, preferably less than 0.5 mm.

[0053] Advantageously, the biocompatible polymer material to be electrospun and / or the electrospinning facilitating agent are as described above.

[0054] According to some embodiments, the composition further comprises a surfactant.

[0055] The surfactant is advantageously a biosurfactant, ie a surfactant of biological and organic origin. In particular, the surfactant is obtained by fermentation of gram-positive microorganisms. Such surfactants have a biological origin, which makes them biocompatible.

[0056] Preferably, the surfactant is selected from lipopeptides, in particular lipopeptides obtained from Bacillus species. More preferably, the surfactant is selected from the surfactin family, in particular from surfactin, pumilacidin and lichenysin.

[0057] Advantageously, the concentration of the surfactant is from 0.1% to 5% by weight, more advantageously from 0.2% to 2% by weight, even more advantageously from 0.5% to 1% by weight, based on the total weight of the fiber.

[0058] According to other embodiments, the composition contains one or more active ingredients selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients.

[0059] Advantageously, the one or more active ingredients are chosen from one or more peptides and their metabolites or derivatives. One class of peptides that can be used as active ingredients are tetrapeptides and their metabolites or derivatives, preferably acetyl tetrapeptides and their metabolites or derivatives. Among the acetyl tetrapeptides, we can mention for example acetyl tetrapeptide-9 and acetyl tetrapeptide-11, which are two anti-aging active compounds that act on the skin matrix to improve its structure and the elasticity and firmness of the skin, respectively.

[0060] According to some embodiments, the one or more active ingredients include mannitol, a pH adjuster such as sodium hydroxide, and / or an anti-wrinkle compound such as aminobutyric acid.

[0061] According to another aspect of the invention, the primary package comprises a hermetically sealed pouch in which the article as described above is enclosed. According to some embodiments, the pouch is composed of two sheets of heat-sealable material welded to each other. Advantageously, the two sheets are welded along their circumference in a manner to form an interior space suitable for accommodating the article.

[0062] According to another aspect of the present invention, a secondary package comprises a box and a plurality of primary packages as described above enclosed in the box. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] These and other aspects, features and advantages of the invention will become apparent from the following description of an embodiment given as a non-limiting example, with reference to the accompanying drawings, in which:

[0064] - Figure 1is a graphical representation of changes in skin moisture content following application of a preparation of the present invention containing a patch product and application of a placebo product;

[0065] - Figure 2 is a graphical representation of changes in skin elasticity following application of a preparation of the present invention containing a patch product and application of a placebo product;

[0066] - Figure 3 is a graphical representation of changes in skin collagen density following administration of a preparation of the present invention comprising a patch product and administration of a placebo product;

[0067] - Figure 4 and Figure 5 is a graphical representation of the changes in the presence of collagen in skin treated with a preparation of the present invention comprising a patch product and compared to untreated skin.

[0068] We must be clear that in this description, the words and terms used, as well as in the various figures of the accompanying drawings as described, have the sole function of better illustrating and explaining the invention, their function being to provide non-limiting examples of the invention itself, since the scope of protection is defined by the claims.

[0069] To facilitate understanding, the same reference numerals are used as much as possible in the drawings to identify the same common elements. It should be understood that elements and features of one embodiment can be conveniently combined or incorporated into other embodiments without further clarification. DETAILED DESCRIPTION

[0070] Unless otherwise defined, all technical and scientific terms used herein and hereinafter have the same meaning as those generally understood by those of ordinary skill in the art to which the present invention belongs. Even if methods and materials similar or equivalent to the methods and materials described herein can be adopted in the practice and test of the present invention, these methods and materials are described only by way of example below. In the event of a conflict, the present application (including its definition) shall prevail. Materials, methods and embodiments are for illustrative purposes only and should not be construed as limiting.

[0071] Unless otherwise stated, all measurements are made at 25°C (ambient temperature) and atmospheric pressure. Unless otherwise stated, all temperatures are in degrees Celsius.

[0072] Unless otherwise indicated, all percentages and ratios reported herein should be understood to relate to weight (w / w) of the total composition.

[0073] Unless otherwise indicated, all percentage ranges reported herein are given with respect to the total of the total composition being 100%.

[0074] Unless otherwise stated, all intervals reported herein should be understood to include the extreme values, including those extreme values ​​where an interval is reported "between" two values.

[0075] Unless otherwise stated, the present specification also includes intervals obtained by merging or overlapping two or more of the intervals.

[0076] Unless otherwise stated, the present specification also includes intervals that can be obtained by combining two or more values ​​taken at different points.

[0077] Unless otherwise stated, reference to water is to be understood as referring to distilled water.

[0078] The article according to the present invention comprises a patch product disposed on a base carrier.

[0079] The patch product is to be applied to the skin and comprises an electrospun membrane matrix consisting of at least one electrospun fiber, in particular at least one nanofiber in the form of a nonwoven fabric. This form is obtained by gradually depositing the fibers on a substrate carrier during the electrospinning process. The fibers are gradually deposited on several layers that gradually overlap. A plurality of fibers can be provided, for example, a plurality of fibers can be delivered simultaneously on the same carrier.

[0080] The base carrier consists of a biodegradable film made of starch, particularly non-genetically modified corn starch. Alternatively, starch from other ingredients such as potato, wheat, cassava, rice, etc. can be used, particularly if they are not genetically modified. It is also conceivable that the base carrier has other layers of other materials combined with the biodegradable starch film.

[0081] The starch used may be of a high amylose type. A high amylose starch is one in which amylose accounts for more than 50% by weight of the starch, in particular more than 60%, more than 75%. For example, the starch may contain about 80% by weight of amylose and 17% by weight of amylopectin. Note that "normal" starch contains about 17% amylose and 80% amylopectin.

[0082] Amylose has a higher concentration, has a substantially linear (unbranched) molecular structure and is longer than amylopectin, favoring the formation of stronger and more stable films.

[0083] Typically, the starch film used for the base carrier may have a thickness of 45 μm to 110 μm, particularly 50 μm to 100 μm, light in color, and provided in the form of a roll having a width of about 1 m. The film has a viscosity of 1.35 g / cm 3 Up to 1.45g / cm 3The present invention relates to a film having a density of 100° C. (measured according to ASTM D 792 standard), a Vicat softening temperature of 130° C. to 135° C. (measured according to ASTM D 1525 standard), a glass transition temperature of 130° C. to 135° C. (measured by DMA method at 50% humidity) and / or a water activity of 0.50 to 0.65 (measured according to PTM03 method). Such water activity values ​​indicate that the starch film has a tendency to absorb water, which causes it to at least partially soften, which facilitates its deformation for better adhesion to the skin in non-planar areas.

[0084] The film advantageously has an elastic modulus of 2000 to 3500 MPa, preferably 2800 to 3000 MPa, a tensile strength of 25 to 60 MPa, preferably 35 to 50 MPa, and a stress at break greater than 20%. These values ​​are measured in the machine direction (MD) according to ASTM D882 standard.

[0085] The film has a static friction coefficient ranging from 0.15 to 0.25, preferably 0.21, and a dynamic friction coefficient ranging from 0.10 to 0.25, preferably equal to 0.17. These friction coefficients are measured according to the STM D1894 standard.

[0086] The film also has a hardness of 100 g / m at 38°C and 75% humidity. 2 / 24 hours to 180g / m 2 / 24 hours, preferably 140g / m 2 / 24 hours water vapor transmission rate (measured according to ASTM E9600 standard), and 1cc.25μm / m at 50% humidity 2 / atm / day to 2cc.25μm / m 2 / atm / day, preferably equal to 1.60cc.25μm / m 2 Oxygen transmission rate / atm / day (measured according to ASTM D1434 standard).

[0087] Advantageously, the base carrier is transparent and allows the dissolution and absorption of the film matrix in the skin to be observed during application. Obviously, this assumes that the film matrix is ​​not transparent. Advantageously, the film has a transparency of 3% to 20%, preferably 6% to 10% (measured according to ASTM D1003 standard), a 60° specular gloss of 70% to 90%, preferably 80% to 85% (measured according to ASTM D2457 standard), and an optical transparency of greater than 85%, preferably greater than 90%, more preferably 95% to 98% (measured according to ASTM D1003 standard).

[0088] Electrospinning is achieved by feeding a specific composition through an electrospinning nozzle under an electric field. The fibers coming out of the electrospinning nozzle are then deposited on a substrate support containing a film made of starch. A nonwoven fabric form can be obtained by relative movement between the electrospinning nozzle and the substrate support.

[0089] Preferably, the fibers are continuous, uniform in composition and have a substantially smooth surface. The fibers are also preferably defect-free, ie free of accumulations or droplets of matrix that may have formed during electrospinning.

[0090] The electrospun fibers may have the shape of flat ribbons, ie, have an oval cross-section.

[0091] Advantageously, the electrospun fibers have a cross-section whose largest transverse dimension is of the order of nanometers and micrometers, but still less than 100 μm, more preferably less than 50 μm, even more preferably less than 25 μm, and of the order of 10 μm at most. The transverse dimension of the matrix fiber may start from 10 nm, for example 50 nm. Note that the transverse dimension remains essentially constant along the entire fiber. An essentially constant transverse dimension means that the diameter may vary, however, the variation does not exceed 30% of the average measured value.

[0092] Fibers with this shape and these dimensions have a greater surface area / volume ratio compared to known fibers, which are usually larger than 100 μm in diameter, as well as better mechanical and structural characteristics that provide higher efficiency and performance compared to industry standards. The large specific surface area of ​​the fibers obtained makes them particularly suitable for the transport and release of active ingredients. The nanofibers obtained allow the use of 1 m 2 / g to 30m 2 / g, preferably 2m 2 / g to 20m 2 / g specific surface area.

[0093] These fibers allow obtaining a membrane matrix that is generally white or in any case light-colored.

[0094] The membrane matrix is ​​made of a biocompatible polymer material capable of being electrospun, and the material is selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, hydroxypropyl methylcellulose HPMC, hydroxypropyl cellulose HPC, hydroxyethyl cellulose HEC, sodium carboxymethyl cellulose Na-CMC, albumin, starch, gelatin, collagen, elastin, β-glucan, chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronic acid HA, galactomannan, xylan, gum arabic, gum ghatti, glucomannan, acemannan, soluble dietary fiber, glycogen, straight-chain starch, and polysaccharides from plants, bacteria and fungi and their derivatives.

[0095] This compound or compounds of this class have the property of being able to modify the viscosity of a liquid, which makes them suitable for forming regular electrospun fibers with good mechanical and absorptive properties. They are also all biocompatible, of natural origin, and can be used in the food, pharmaceutical and / or cosmetic industries.

[0096] In particular, xanthan gum, dextran, carrageenan, Na-CMC, starch, gelatin and gum ghatti are used as thickeners, stabilizers and possibly gelling agents in the food industry. In addition, xanthan gum is used as a stabilizer for suspensions and emulsions in the pharmaceutical and cosmetic industries, guar gum is also used as a thickener and gelling agent in the pharmaceutical and cosmetic industries, and carrageenan is used as an inactive excipient in the pharmaceutical industry. Dextran is also used as a thickener in the pharmaceutical industry.

[0097] Chitosan is used as an excipient in the food industry, in low-calorie diets and in the pharmaceutical industry, especially for products to be inhaled. Pectin, on the other hand, is used as a gelling agent in the food industry and as a dietary and probiotic agent in the pharmaceutical industry.

[0098] Agar, galactomannan and glucomannan are used as gelling agents in the nutritional industry.

[0099] Among cellulose derivatives, HPMC is used as a stabilizer and viscosity regulator in the food industry and as an excipient for eye drops or oral medications in the pharmaceutical industry. HPC is used as a food additive and as an eye drop or tablet binder in the pharmaceutical industry. HEC is used as a thickener and gelling agent in the pharmaceutical and cosmetic industries.

[0100] Beta-glucan is commonly used as a dietary fiber, as is xylan. Chondroitin sulfate is used as a dietary supplement and is also used to treat symptoms of osteoarthritis. Dermatan sulfate, heparin, and heparan sulfate are known in the pharmaceutical industry as anticoagulants.

[0101] Gum Arabic is used as a stabilizing excipient and viscosity modifier in the food industry. On the other hand, acemannan is known in the pharmaceutical industry for its immunostimulatory properties.

[0102] It should be noted that some of these compounds have their own functions in the cosmetic, pharmaceutical or food industries, such as starch, elastin, hyaluronic acid, heparin, collagen, pectin, β-glucan, chondroitin sulfate, dermatan sulfate, heparan sulfate and its derivatives, etc. Therefore, electrospinning these compounds is advantageous because the application of the corresponding fibers will allow these compounds to be applied in larger doses than in known solutions, making them more effective.

[0103] If the biocompatible polymer material to be electrospun is hyaluronic acid, it can be of the linear or cross-linked type and can be of high mass, for example of the order of one million Daltons or even higher, or of low mass, typically of the order of 10,000 Daltons or lower. It is also possible to provide a mixture of linear hyaluronic acid and cross-linked hyaluronic acid in order to adjust the stiffness of the yarn to be obtained, as well as the three-dimensional structure of the film that can be obtained by depositing the yarn on a support.

[0104] At least one electrospinning facilitator is also included in the composition of the membrane matrix, and the electrospinning facilitator is an uncharged carrier polymer with good biocompatibility. The electrospinning facilitator is selected from alginate (possibly in the presence of PEO) and pullulan. The spinning facilitator is preferably pullulan because it allows to achieve the best results.

[0105] If alginate is mixed with PEO, they can be diluted in an aqueous or water-based solution, respectively, at a concentration of 0.1 wt % to 30 wt %, preferably 1 wt % to 20 wt %, more preferably 5 wt % to 15 wt %. If a PEO mixture is present, the alginate:PEO mixture is made in a weight ratio of preferably 5:1 to 1:5, more preferably 2:1 to 1:2. A weight ratio of 1:1 is used to obtain the best electrospinning results.

[0106] Pullulan may be diluted in an aqueous or water-based solution, preferably in a concentration of 0.1 wt % to 30 wt %, preferably 1 wt % to 20 wt %, more preferably 5 wt % to 15 wt %.

[0107] The polymer material to be electrospun and the accelerator are mixed in the following ratios: (first compound): accelerator by weight preferably 10:1 to 1:10, more preferably 5:1 to 1:5, even more preferably 2:1 to 1:2. It can be confirmed that the best results can be obtained with a composition in which the weight ratio of the first compound to the accelerator is equal to 1:1.

[0108] The film matrix also contains a surfactant selected from biosurfactants, ie surfactants of biological and organic origin as opposed to surfactants of bacterial origin.

[0109] In particular, the surfactant of the composition is advantageously obtained by fermentation of Gram-positive microorganisms.

[0110] More precisely, the biosurfactant is chosen from lipopeptides, in particular lipopeptides derived from the fermentation of organisms of the genus Bactillus, more particularly lipopeptides with a low molecular weight, for example a molecular weight of at most 10000 g / mol, preferably at most 5000 g / mol, more preferably at most 2500 g / mol.

[0111] There are several families among these lipopeptides, such as surfactin, iturin, fengycin, kurstatin and locimycin. These lipopeptide families are distinguished from each other by the type and sequence of amino acid residues, the nature of the peptide cycle and the nature, length and branching of the fatty acid chain. However, all of them have surfactant properties.

[0112] Preferably, the biosurfactant of the composition is selected from the surfactin family.

[0113] In the surfactin family, there is surfactin itself, which can be produced by different branches of Bacillus species, especially Bacillus subtilis, but also by other branches, such as B. natto or B. circulans. Their structure consists of seven amino acids with a characteristic chiral sequence (L-Glu, L-Leu, D-Leu, L-Val, L-Asp, D-Leu and L-Leu, where the first and last amino acids are connected by ester bonds to form a lactone ring). Surfactin has a β-hydroxy fatty acid chain with a length of thirteen to sixteen carbon atoms. Although more than 30 homologs are known in surfactin, they all have the same LLDLLDL chiral amino acid sequence in the lactone ring. Homologs refer to molecules that belong to the same species but are not isomers.

[0114] The surfactin family also includes Pumiliacidin obtainable by a B. pumilus clade with variants AF. Compared to surfactin, the amino acid at position 7 is substituted by L-Val or L-Ile.

[0115] Finally, the surfactin family includes lichenin, obtained primarily from B. licheniformis, which differs from surfactin by substitution of L-glutamine at position 1 of the L-glutamic acid lactone ring.

[0116] Surfactin, Pumiliacidin and lichenin contain five hydrophobic residues (Leu, Val or Ile) and long secondary fatty chains, giving them powerful surfactant properties. In fact, it has been demonstrated that high-purity surfactant family compounds can reduce the surface tension of water from 72mN / m to 27mN / m at a concentration of 0.0005% by weight. Surfactin is stable and soluble in water over a wide pH (5-13) and temperature range, making them particularly suitable for electrospinning in aqueous solutions.

[0117] Preferably, the biosurfactant is surfactant or biosurfactin.

[0118] Typically, the biosurfactant is present in a concentration of less than 5%, preferably less than 2%, more preferably from 0.5% to 1% by weight based on the weight of the composition.

[0119] Preferably, the composition also comprises at least one active ingredient of the pharmaceutical, nutritional and / or cosmetic type.

[0120] It should be noted that, regardless of the field of action, an active ingredient can have multiple types of functions.

[0121] The cosmetic active ingredients can be of the following types: anti-seborrhea agents (e.g., sebacic acid, azelaic acid), anti-sebum agents (e.g., coal powder), antibacterial agents (e.g., climbazole, pyroctone olamine salt, olamine), antioxidants (e.g., ascorbic acid, tocopherol, coenzyme Q10, resveratrol, glutathione), antiperspirants (e.g., aluminum chlorohydrate, aluminum sesquichlorohydrate), astringents (e.g., orange flower extract, calcium lactate), bleaching agents (e.g., glabridin, ammonium persulfate), makeup removers (e.g., sodium cocoyl glutamate), deodorants (e.g., triethyl citrate, zinc ricinoleate), exfoliants (e.g., glycolic acid, malic acid, mandelic acid), flavoring agents (e.g., citral, honey), fragrances (e.g., d,l-limonene, coumarin), humectants (e.g., glycerin, propylene glycol), keratolytic agents (e.g., chloroacetic acid, salicylic acid), moisturizers (e.g., aloe arborescens leaf extract), Fragrances (e.g., geraniol, linalool), emollients (e.g., triolein, squalene), refreshing agents (e.g., menthol, menthyl lactate), skin moisturizers (e.g., panthenol, allantoin), skin protectants (e.g., sphingolipids, zinc oxide), smoothing agents (e.g., castor seed oil), soothing agents (e.g., extracts of witch hazel, chamomile extract, bisabolol) or tonics (e.g., arnica, capsicum extract), UV filters (e.g., methylene bisbenzotriazolyl tetramethylbutylphenol, ethylhexyl methoxycinnamate, caffeine, caffeine, theobromine, theophylline), anti-wrinkle agents (e.g., aminobutyric acid), one or more peptides and their metabolites and derivatives (e.g., essential amino acids and branched-chain amino acids, tetrapeptides).

[0122] The active pharmaceutical ingredient may be of the following types: 5-α-reductase inhibitors (e.g., finasteride), 5-aminosalicylate (e.g., mesalazine), 5HT3 receptor antagonists (e.g., ondansetron), ACE inhibitors containing calcium channel blockers (e.g., amlodipine / benazepril), ACE inhibitors containing thiazides (e.g., hydrochlorothiazide), adamantane antiviral agents (e.g., amantadine), adrenocorticosteroid inhibitors (e.g., aminoglutethimide), adrenergic bronchodilators (e.g., salbutamol), hypertensive emergency therapeutic agents (e.g., diazoxide), pulmonary hypertension therapeutic agents (e.g., treprostinil), aldosterone receptor antagonists (e.g., spironolactone), alkylating agents (e.g., cyclophosphamide), allergens ( For example, house dust mite allergen extracts), alpha-glucosidase inhibitors (e.g., miglitol), anti-amoebic drugs (e.g., metronidazole), aminoglycosides (e.g., tobramycin), aminopenicillins (e.g., amoxicillin), aminosalicylates (e.g., aminosalicylic acid), AMPA receptor antagonists (e.g., perampanel), amylin analogs (e.g., pramlintida), analgesics (e.g., acetaminophen), androgens and anabolic steroids (e.g., testosterone), angiotensin converting enzyme inhibitors (e.g., ramipril), angiotensin II inhibitors containing calcium channel blockers (e.g., amlodipine / olmesartan), angiotensin II inhibitors containing thiazides (e.g., hydrochlorothiazide / olmesartan), angiotensin receptor blockers (e.g., valsartan), angiotensin receptor blockers and neprilysin inhibitors (e.g., sacubitril / valsartan), anorectal preparations (e.g., hydrocortisone / pramoxine), anorectal agents (e.g., phentermine), antacids (e.g., magnesium hydroxide), anthelmintics (e.g., pyrantel), antiangiogenic ophthalmic agents (e.g., aflibercept), anti-CTLA-4 monoclonal antibodies (e.g., ipilimumab), anti-PD-1 monoclonal antibodies (e.g., nivolumab), thiazide-containing antiadrenergic agents (central) (e.g., hydrochlorothiazide / methyldopa), thiazide-containing antiadrenergic agents (peripheral) (e.g., polythiazide / prazosin), centrally acting antiadrenergic agents adrenergic agents (e.g., guanfacine), peripherally acting antiadrenergic agents (e.g., tamsulosin), antiandrogens (e.g., enzalutamide), antianginal agents (e.g., nitroglycerin, diprophylline / guaifenesin), antibiotics (e.g., metronidazole), antibiotic / antineoplasty agents (e.g., doxorubicin), anticholinergic antiemetics (e.g., diphenhydramine), anticholinergic antiparkinsonian agents (e.g., procyclidine), anticholinergic bronchodilators (e.g., thiotropin), anticholinergic / spasmodics (e.g., scopolamine), anticoagulants (e.g., phytonadione), anticonvulsants (e.g., lacosamide), antidepressants (e.g., bupropion), antidiarrheals (e.g., loperamide), antidiuretic hormones (e.g.,desmopressin), antidotes (e.g., naltrexone, dronabinol), antifungals (e.g., griseofulvin), antigonadotropins (e.g., danazol), antigout (e.g., colchicine), antihistamines (e.g., cetirizine), antihyperlipidemics and combinations (e.g., ezetimibe / simvastatin), antihyperuricemics (e.g., febuxostat), antimalarials (e.g., doxycycline), antimalarial combinations, antimalarial quinolines (e.g., hydroxychloroquine), antimanics (e.g., lithium), antimetabolites (e.g., capecitabine), antimigraines (e.g., rizatriptan), antineoplastics (e.g., isotretinoin), antineoplastic combinations (e.g., letrozole / ribociclib), antineoplastic antidotes (e.g., amifostine), antineoplastic interferons ( For example, interferon alfa-2b), antipseudomonal penicillins (e.g., carbenicillin), antipsoriatics (e.g., acitretin), antipsychotics (e.g., haloperidol), antirheumatic drugs (e.g., adalimumab), antiseptics and antiseptics, antithyroid drugs (e.g., potassium iodide), antitoxins and antivirals (e.g., polyvalent antivenom (Crothaleridae)), cough suppressants (e.g., dextromethorphan), antiviral boosters (e.g., ritonavir), antiviral interferons (e.g., peginterferon alfa-2a), aromatase inhibitors (e.g., anastrozole), atypical antipsychotics (e.g., aripiprazole), azole antifungals (e.g., fluconazole), bacterial vaccines (e.g., 13-valent pneumococcal vaccine) , barbiturate anticonvulsants (e.g., primidone), barbiturates (e.g., phenobarbital), BCR-tyrosine kinase inhibitor ABL (e.g., imatin), benzodiazepine anticonvulsants (e.g., diazepam), benzodiazepines (e.g., clonazepam), thiazide-containing beta-blockers (e.g., bisoprolol / hydrochlorothiazide), beta-lactamase inhibitors (e.g., clavulanic acid), bile acid sequestrants (e.g., colesevelam), bisphosphonates (e.g., zoledronic acid), BTK inhibitors (e.g., ibrutinib), calcimimetics (e.g., cinacalcet), calcineurin inhibitors (e.g., tacrolimus), calcitonin, calcium channel blockers (e.g., verapamil), carbamate anticonvulsants (e.g., felbamate), carbapenems (e.g., doripenem), carbapenem / β-lactamase inhibitors (e.g., meropenem / vaborbactam), carbonic anhydrase inhibitors anticonvulsants (e.g., topiramate), carbonic anhydrase inhibitors (e.g., acetazolamide), regenosadase stress agents, cardioselective β-blockers (e.g., nebivolol), catecholamines (e.g., epinephrine), monoclonal antibody CD20 (e.g., ocrelizumab), monoclonal antibody CD30 (e.g., brentuximab), monoclonal antibody CD33 (e.g., gemtuzumab), monoclonal antibody CD38 (e.g., monoclonal CD52, alemtuzumab), CDK 4 / 6 inhibitors (e.g.,palbociclib), cephalosporins / β-lactamase inhibitors (e.g., avibactam / ceftazidime), cerumenolytics (e.g., carbamide peroxide), CFTR combinations (ivacaftor / lumacattor), CFTR enhancers (e.g., ivacaftor), CGRP inhibitors (e.g., efenafil), chelators (e.g., deferasirox), chemokine receptor antagonists (e.g., maraviroc), chloride channel activators (e.g., lubiprostone), cholesterol absorption inhibitors (e.g., ezetimibe), cholinergic agonists (e.g., cevimeline), cholinergic muscle stimulants (e.g., pyridostigmine), cholinesterase inhibitors (e.g., donepezil), central nervous system stimulants (e.g., phentermine), colony-stimulating factors (e.g., filgrastim), birth control pills (e.g., levonorgestrel), corticotropins, coumarins, and indanediones (e.g., warfarin), COX-2 inhibitors (e.g., celecoxib), decongestants (e.g., pseudoephedrine), diarylquinolines, benzodiazepine anticonvulsants (e.g., carbamazepine), digestive enzymes (e.g., lactase), dipeptidyl peptidase 4 inhibitors (e.g., sitagliptin), dopaminergic antiparkinsonian drugs (e.g., ropinirole), drugs for alcohol dependence (e.g., acamprosate), echinocandins (e.g., caspofungin), inhibitors (e.g., erlotinib), estrogen receptor antagonists (e.g., fulvestrant), estrogens (e.g., estradiol), expectorants (e.g., guaifenesin), factor Xa inhibitors (e.g., rivaroxaban), drug-derived anticonvulsant fatty acids (e.g., divalproex sodium), fibric acid derivatives (e.g., fenofibrate), first-generation cephalosporins (e.g., cephalexin), fourth-generation cephalosporins (e.g., cefepime), gallstone dissolving agents (e.g., ursodeoxycholic acid), gamma-aminobutyric acid analogs (e.g., gabapentin), gamma-aminobutyric acid reuptake inhibitors (e.g., tiagabine), general anesthetics (e.g., propofol), gastrointestinal stimulants (e.g., metoclopramide), glucocorticoids (e.g., budesonide), hyperglycemic agents (e.g., glucagon), glycopeptide antibiotics (e.g., vancomycin), platelet glycoprotein inhibitors (e.g., tirofiban) , glycylcyclines (e.g., tigecycline), gonadotropin-releasing hormones (e.g., leuprolide), gonadotropin-releasing hormone antagonists (e.g., elagolix), gonadotropins (e.g., chorionic gonadotropin), group I antiarrhythmics (e.g., phenytoin), group II antiarrhythmics (e.g., propranolol), group III antiarrhythmics (e.g., dronedarone), group IV antiarrhythmics (e.g., verapamil), group V antiarrhythmics (e.g., digoxin), growth hormone receptor blockers (e.g., pegvisomant), growth hormones (e.g., somatropin), guanylate cyclase-C agonists (e.g., linaclotide), Helicobacter pylori (H. pylori) eradication agents (e.g.,Potassium bismuth citrate / metronidazole / tetracycline), H2 antagonists (e.g., ranitidine), hedgehog pathway inhibitors (e.g., vismodegib), heparin antagonists (e.g., protamine), HER2 inhibitors (e.g., neratinib), herbal products (e.g., 5-hydroxytryptophan, aloe vera), histone deacetylase inhibitors (e.g., romidepsin), hormones / antineoplastic agents (e.g., medroxyprogesterone), hydantoin anticonvulsants (e.g., phenytoin), hydrazide derivatives (e.g., isoniazid), immunoglobulins, impotence drugs (e.g., sildenafil), incretin mimetics (e.g., liraglutide), inotropes (e.g., digoxin), insulin and its derivatives (e.g., insulin glargine), insulin-like growth factors (e.g., mecasermin), interferons (e.g., interferon beta-1a), interleukin inhibitors (e.g., dupilumab), interleukins (e.g., aldesleukin), iron products (e.g., sulfhydryl esters), ferrous acid), ketolides (e.g., telithromycin), laxatives (e.g., bisacodyl), antileprosy drugs (e.g., clofazimine), leukotriene modifiers (e.g., montelukast), lincomycin derivatives (e.g., clindamycin), loop diuretics (e.g., furosemide), lysosomal enzymes (e.g., imiglucerase), macrolides (e.g., azithromycin), mast cell stabilizers (e.g., cromolyn), meglitinides (e.g., repaglinide), melanocortin receptor agonists (e.g., bremelanotide), methylxanthines (e.g., theocorticoids), mineralocorticoids (e.g., fludrocortisone), minerals and electrolytes (e.g., citric acid / potassium citrate), ), various antiviral drugs (e.g., mabaloxavir), various anxiolytics, sedatives, and hypnotics (e.g., zolpidem), various bone resorption inhibitors (e.g., denosumab), various cardiovascular drugs (e.g., midodrine), various central nervous system drugs (e.g., dalfampridine), various coagulation regulators (e.g., tranexamic acid), various diuretics (e.g., pamabrom), various genitourinary drugs (e.g., phenazopyridine), various gastrointestinal drugs (e.g., misoprostol), various metabolic drugs (e.g., burosumab), various respiratory drugs (e.g., α1-proteinase inhibitors), various topical drugs (e.g., (e.g., sodium hyaluronate), various vaginal agents (e.g., estradiol), mitotic inhibitors (e.g., vincristine), monoamine oxidase inhibitors (e.g., phenelzine), oral and throat products (e.g., fluoride), mTOR inhibitors (e.g., everolimus), mucolytics (e.g., acetylcysteine), multikinase inhibitors (e.g., sorafenib), combination narcotic analgesics (e.g., buprenorphine / naloxone), narcotic analgesics (e.g., fentanyl), natural penicillins (e.g., penicillin V potassium), neuraminidase inhibitors (e.g., oseltamivir), neuronal potassium channel openers (e.g., eszogabine), new generation cephalosporins (e.g.,ceftaroline), NHE3 inhibitors (e.g., ceftaroline), niacin (e.g., ethionamide), NK1 receptor antagonists (e.g., aprepitant), NNRTIs (e.g., efavirenz), non-cardioselective beta-blockers (e.g., carvedilol), non-sulfonylureas (e.g., metformin), nonsteroidal anti-inflammatory drugs (e.g., diclofenac), NS5A inhibitors (e.g., daclatasvir), nucleoside reverse transcriptase inhibitors (NRTIs) (e.g., tenofovir), nutraceuticals (e.g., omega-3 polyunsaturated fatty acids), oral dietary supplements (e.g., arginine), other immunostimulants (e.g., glatiramer), other immunosuppressants (e.g., omalizumab), oxazolidinedione anticonvulsants (e.g., trimethadione), oxazolidinone antibiotics (e.g., linezolid), PTH and its analogs (e.g., teriparatide), PARP inhibitors (e.g., niraparib), PCSK9 inhibitors (e.g., evolocumab), anti-penicillinase penicillins (e.g., oxacillin), peripheral opioid receptor antagonists (e.g., naloxegol), mixed peripheral opioid receptor agonists (agonist / antagonist isadorelin), peripheral vasodilators (e.g., isoxazolidinone), peripherally acting weight loss drugs (e.g., orlistat), phenothiazine antiemetics (e.g., promethazine), phenothiazine antipsychotics (e.g., prochlorperazine), phenylpiperazine antidepressants (e.g., trazodone), potassium phosphate inhibitors ( (e.g., trazodone, idelalisib), platelet aggregation inhibitors (e.g., aspirin), platelet stimulants (e.g., eltrombopag), polyenes (e.g., nystatin), potassium-sparing diuretics (e.g., spironolactone), probiotics (e.g., Lactobacillus acidophilus), modulator receptor inhibitors (e.g., ulipristal), progestins (levonorgestrel), prolactin inhibitors (e.g., cabergoline), protease inhibitors (e.g., telaprevir), protease-activated receptor-1 antagonists (e.g., vorapaxar), proteasome inhibitors (e.g., bortezomib), proton pump inhibitors (e.g., omeprazole), psoralens (e.g., methoxsalen), purine nucleosides (e.g., valacyclovir), pyrrolidine anticonvulsants (e.g., levetiracetam, racetam), quinolones (e.g., ciprofloxacin), recombinant human erythropoietin (e.g., epoetin alfa), renin inhibitors (e.g., aliskiren), rifamycin derivatives (e.g., rifampicin), salicylates (e.g., aspirin), second-generation cephalosporins (e.g., selective cefuroxime receptor), modulators (e.g., ospemifene), selective immunosuppressants (e.g., natalizumab), selective phosphodiesterase-4 inhibitors (e.g., roflumilast), selective serotonin reuptake inhibitors (e.g., escitalopram), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine), serotonergic neuromodulators (e.g., tegaserod), SGLT-2 inhibitors (e.g.,empagliflozin), skeletal muscle relaxants (e.g., botulinum toxin type A), smoking cessation agents (e.g., nicotine analogs somatostatin, octreotide), statins (e.g., lovastatin), streptogramins (e.g., dalfopristin / quinupristin), Streptomyces derivatives (e.g., capreomycin), anticonvulsants succinimides (e.g., ethosuximide), sulfonamides (e.g., sulfamethoxazole), sulfonylurea agonists (e.g., glimepistole, clomiphene), tetracyclic antidepressants (e.g., mirtazapine), tetracyclines (e.g., minocycline), thiazide diuretics (e.g., hydrochlorothiazide), thiazolidinediones (e.g., pioglitazone), thioxanthines (e.g., ezetimibe), vorthixene), third-generation cephalosporins (e.g., ceftriaxone), thrombin inhibitors (e.g., dabigatazone), streptolytic agents (e.g., levothyroxine), TNFα inhibitors (e.g., adalimumab), tocolytics (e.g., terbutaline), topical acne medications (e.g., tretinoin), local anesthetics (e.g., lidocaine), topical anti-infectives (e.g., malathion), topical anti-rosacea medications (e.g., ivermectin), topical antibiotics (e.g., silver sulfadiazine), topical antifungals (e.g., econazole), topical antihistamines (e.g., diphenhydramine), topical antineoplastic agents (e.g., imiquimod), topical anti-silver Psoriasis drugs (e.g., tazarotene), topical antivirals (e.g., penciclovir), topical astringents (e.g., hazelnut), topical debridements (e.g., collagenase), topical depigmenting agents (e.g., hydroquinone), topical emollients (e.g., emollients), topical keratolytics (e.g., salicylic acid), topical nonsteroidal anti-inflammatory drugs (e.g., diclofenac), topical photochemicals (e.g., aminolevulinic acid), topical rubefacients (e.g., menthol), topical steroids (e.g., betamethasone), topical steroids with anti-infectives (e.g., acyclovir / hydrocortisone), transthyretin stabilizers (e.g., tamiflu), triazine anticonvulsants (e.g., lamotrigine) , tricyclic antidepressants (e.g., amitriptyline), urea cycle disruptors (e.g., sodium phenylbutyrate), urinary anti-infectives (e.g., nitrofurantoin), urinary antispasmodics (e.g., amitriptyline), modulators (e.g., potassium citrate), uterotonics (e.g., dinoprostone), vaginal anti-infectives (e.g., clindamycin), vasodilators (e.g., alprostadil), vasopressin antagonists (e.g., conivaptan), vasopressors (e.g., epinephrine), VEGF / VEGFR inhibitors (e.g., pazopan), viral vaccines, vitamin and mineral combinations, vitamins (e.g., cyanocobalamin), VMAT2 inhibitors (e.g., valbenazine).

[0123] The nutritionally active ingredients can be of the following types: vitamins (e.g., vitamins A, B, C, D, E, K, folic acid, biotin), minerals (e.g., potassium, chloride, sodium, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, chromium, molybdenum, selenium, cobalt, fluoride), amino acids, peptides and proteins and their metabolites and derivatives (e.g., essential and branched-chain amino acids, carnosine, enzymes and enzyme complexes, lactoferrin, N-acetylcysteine, proteins from animal or plant foods), fatty acids (e.g., omega-3, omega-6, omega-9 fatty acids), Natural products derived from whole sources or substances of plants, animals, algae, fungi, lichens, or bacteria (e.g., phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, digestive enzymes derived from mushrooms), sugars and polysaccharides (e.g., mannose, ribose, trehalose, glucose, glucuronolactone, dextrins), probiotics (e.g., live microorganisms such as Lactobacillus species, Bifidobacterium species, Saccharomyces boulardii boulardii), prebiotics (e.g., fructans such as oligofructose and inulin, galactans such as galacto-oligosaccharides and oligoxylose), antioxidants (e.g., lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins), other substances with nutritional or physiological effects (e.g., betaine, caffeine, theobromine, theophylline, CDP-choline, choline, creatine, phospholipids, GABA, glucosamine, inositol, melatonin, methylsulfonylmethane, nucleotides, squalene).

[0124] The active ingredient can be included in the electrospun fibers by co-electrospinning the active ingredient with the biocompatible polymer material, the facilitator and, if present, the surfactant. In this case, a mixture of the polymer material to be electrospun and the electrospinning facilitator and the active ingredient can be prepared, possibly in the presence of a surfactant, and the obtained mixture is electrospun.

[0125] Alternatively, the biocompatible polymer material, the enhancer and the surfactant can be electrospun first and the active ingredient subsequently integrated into the resulting fibers. Depending on the application, the active ingredient can be absorbed into the electrospun fibers or entrapped in the three-dimensional structure obtained with electrospun fibers.

[0126] For example, the polymer material to be electrospun may comprise a mixture of linear hyaluronic acid and cross-linked hyaluronic acid. The cross-linked hyaluronic acid not only has the effect of improving the stiffness of the resulting nanofibers, but also increases the complexity of the three-dimensional structure of the film obtained by continuously depositing the resulting fibers on multiple layers. In particular, the presence of cross-linked hyaluronic acid results in the formation of cavities in the film that allow the accommodating of active ingredient molecules.

[0127] According to another example, the active ingredient is a non-steroidal anti-inflammatory drug, which will be applied, for example, to skin burns. One or more analgesics may also be added as additional active ingredients to relieve the pain caused by the burn. For this type of application, it is particularly advantageous that the biocompatible polymer material is of the type used for skin regeneration, such as hyaluronic acid.

[0128] The preparation according to the invention can be advantageously used for treating skin burns. This is advantageous because it allows the active ingredient as well as the first compound to be absorbed quickly into the wound. Furthermore, the product obtained by electrospinning the composition can be applied directly to the burn area. This increases the effectiveness of the treatment.

[0129] Advantageously, the active ingredient is present in a concentration of 0.1% to 30% by weight, more preferably 0.2% to 20% by weight, even more preferably 0.5% to 10% by weight.

[0130] Note that hyaluronic acid, as the compound to be electrospun, is a good candidate for combination with several active ingredients, which are each of the three types mentioned above.

[0131] For example, among the cosmetic active ingredients, the following may be mentioned: anti-seborrhea agents (sebacic acid, azelaic acid), antioxidants (ascorbic acid, tocopherol, retinol, retinal), anti-pigmentation agents (glabridin, ammonium persulfate), emollients (extracts of witch hazel, bisabolol) and humectants (e.g. glycerol, propylene glycol), anti-wrinkle agents (e.g. aminobutyric acid), and one or more peptides and their metabolites and derivatives (e.g. essential amino acids and branched-chain amino acids, tetrapeptides).

[0132] Among the preferred nutritional active ingredients are natural products made using whole sources or substances extracted or derived from plants, animals, algae, fungi, lichens or bacteria (phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, fungus-derived digestive enzymes), vitamins (e.g., vitamins A, B, C, D, E, K, folic acid, biotin) and antioxidants (e.g., lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins).

[0133] The most favorable pharmaceutical active ingredients are androgens and anabolic steroids (e.g., testosterone), anti-CTLA-4 monoclonal antibodies (e.g., ipilimumab), anti-PD-1 monoclonal antibodies (e.g., nivolumab), antianginal drugs (e.g., nitroglycerin), antiasthmatic drug combinations (e.g., diprophylline / guaifenesin), antibiotics (e.g., metronidazole), antibiotic / antineoplastics (e.g., doxorubicin), antineoplastics (e.g., isotretinoin), and antineoplastic combinations (e.g., letrozole / ribociclib).

[0134] One example of a patch product includes a membrane matrix composed of electrospun fibers obtained from a composition comprising sodium hyaluronate as a source of hyaluronic acid, pullulan as an electrospinning accelerator, and mannitol, sodium surfactant as a surfactant, aminobutyric acid, acetyl tetrapeptide-9, and acetyl tetrapeptide-11. This patch product is particularly suitable for application to facial skin, especially for skin rejuvenation.

[0135] Note that such active ingredients can advantageously be combined with other compounds to be electrospun, such as xanthan gum, guar gum, chondroitin sulfate, collagen or starch.

[0136] Another example of a patch product is based on heparin and a pharmaceutically active ingredient, such as an allergen extract or a platelet stimulator, such as eltrombopag, as an electrospun compound.

[0137] According to some embodiments, the patch product further comprises a stabilizer, which is preferably a cross-linkable polymer. An example of a stabilizer is sodium alginate, which should be added to the pullulan as a promoter. Preferably, the ratio of pullulan: alginate is 3:1.5 to 3:0.5, more preferably 3:1.

[0138] Once the article is made, it can be closed by applying a cover sheet on the base carrier. The cover sheet is connected to the base carrier by gluing or welding. The sheet can be the same material as the base carrier, or it can be made of another polysaccharide or another starch, or it can be made of materials known in the art, such as polybutylene succinate-adipate PBSA or polylactic acid PLA.

[0139] The article (i.e., the film matrix and base carrier assembly) may also be packaged in a pouch of known type, which is made, for example, of two sheets of heat-sealable material such as PBSA or PLA, which are welded to each other to form an airtight sealed interior space in which the article is enclosed.

[0140] The articles may be packaged in a secondary package such as a box comprising a plurality of pouches, each pouch enclosing a respective article as described above.

[0141] The use of the preparation provides, in a preliminary step, humidification of the skin area corresponding to the application of the product. The sachet is then opened, the patch product is removed, taking care to only contact the polysaccharide carrier to avoid damaging the film matrix, and then the patch product is applied to the moistened area of ​​the skin, with the film matrix in direct contact with the skin. Due to the hydrating effect imparted by the polysaccharide carrier, combined with the hydrating effect of the film matrix, and the adaptability of the carrier shape, the film matrix is ​​quickly and completely absorbed by the skin. The carrier is kept on the skin for a few seconds, the amount of time for the absorption of the film matrix to be completed, and then it is removed. Note that during this time, even if it is short, the polysaccharide carrier has a hydrating effect on the skin.

[0142] Example

[0143] Thirty volunteers were evaluated and asked to apply a cosmetic patch product according to the preparation of the present invention and a placebo.

[0144] Each volunteer applied the cosmetic product and a placebo on their respective arm (specifically the palmar area of ​​the forearm) once a day for four months.

[0145] The cosmetic products and placebo were provided in the form of electrospun fiber sheets, approximately 10 cm in size. 2 , on a non-genetically modified corn starch base carrier with a high amylose content.

[0146] The cosmetic product used contains hyaluronic acid HA as the biocompatible polymer material to be electrospun and pullulan as an electrospinning accelerator. 25 g of hyaluronic acid, 12.5 g of pullulan and 1 g of biosurfactant are dissolved in 30 mL-50 mL of water and diluted to a volume of 100 mL, the pH is controlled and possibly corrected by adding 1 M NaOH solution to obtain a pH of 5.5-6 to prepare an electrospinning solution.

[0147] On the other hand, the placebo contained only pullulan without hyaluronic acid. Similar to what is described for the cosmetic product, 15 g of pullulan was dissolved in 30 mL-50 mL of water and made to 100 mL for dilution, the pH was controlled and possibly corrected by adding 1 M NaOH solution to obtain a pH of 5.5-6. The obtained solution was then electrospun.

[0148] The treatment effect was measured instrumentally, in particular the skin hydration content, skin elasticity and collagen density were assessed. The measurements were performed before the start of the treatment (T0) and after 1 month (T1), 2 months (T2) and 3 months (T3).

[0149] Assessment of skin hydration

[0150] Skin moisture content was measured using a Derma Unit SSC 3 instrument from Courage+Khazaka, in which Moisture detection probe. The probe consists of a series of gold metal tracks that act as the plates of a capacitor. The plates are electrically isolated by an electrical insulator called a dielectric. After being connected to a power source, electrons flow between the plates, creating an electric field: the amount of charge stored by the capacitor is called the capacitance. Most materials have a dielectric constant greater than that of a vacuum, so that any material between the capacitor plates increases the capacitance. The presence of water in the skin causes a change in capacitance that is proportional to its content, thus measuring the skin's hydration level in arbitrary units.

[0151] Assessment of skin elasticity

[0152] Skin elasticity is measured with a DermaLab Combo Skinlab elasticity probe purchased from Cortex. The probe is equipped with a chamber in which a vacuum is applied and which allows suction to be applied on the skin surface. The suction method includes a skin lifting step and a skin retraction step, which are controlled by an infrared sensor in the probe chamber. One of the parameters related to skin elasticity is the retraction time, which represents the time required for the skin to retract 1.5 mm after the maximum lifting point has been reached, expressed in milliseconds. Young, elastic skin will quickly return to its original state when lifted, while less elastic skin will have a longer retraction time. Therefore, a reduction in the retraction time indicates an increase in skin elasticity.

[0153] Assessment of collagen density

[0154] High-resolution images of the deeper layers of the skin are obtained using the DermaLab Combo Skinlab ultrasound probe (Cortex). The technology is based on measuring the acoustic response of the skin when an acoustic pulse of known frequency is sent into the skin itself. This acoustic pulse hits different structures of the skin and is partially reflected. The reflected signal is partially picked up by the ultrasound transducer and processed to provide a cross-sectional image of the skin. The intensity of the reflected signal is represented by a color scale, where the darkest areas represent areas with low response (those areas where the density of the structure is low or absent), while the brighter areas represent areas with higher density. This technology allows the reconstruction of skin images up to 3.4mm deep with a resolution of 0.06mm, highlighting the structures of the epidermis, dermis and subcutaneous layers. The image processing software provides an intensity value of the echo response that is directly related to the collagen density. The energy of the acoustic pulses used is very low and has no negative impact on the skin and other tissues.

[0155] analyze

[0156] The measurements were performed in a temperature-controlled environment at 21 ± 2 °C and humidity of approximately 50%. Volunteers were allowed to acclimate to the environment for 15 minutes before each measurement.

[0157] The application of the cosmetic product and placebo provides moisturization of the skin corresponding to the area to be treated, applying the product sheet with the base carrier facing upwards, leaving the product to be moisturized so that it adheres well to the skin, removing the base carrier and, if necessary, gently patting the treated area so that the product is completely absorbed.

[0158] result

[0159] The results of the treatments in terms of skin moisture content are summarized in Tables 1 and Figure 1 The skin moisture content measurements expressed in arbitrary units of corneometry are reported as the average of the values ​​recorded during the test, as the difference and percentage change between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2) and 3 months (T3). The skin area not treated (with cosmetics or placebo) was arbitrarily determined as the control area.

[0160]

[0161] The treatment with the cosmetic product showed a significant increase in the skin's water content after 1, 2 and 3 months, equal to 6.8%, 18.9% and 17.9%, respectively. No significant changes were observed in the placebo group and in the control area.

[0162] The results on skin elasticity are summarized in Table 2 and are presented in Figure 2 The elasticity data, expressed in milliseconds (msec), are reported as the average of the values ​​recorded during the test, as the difference and percentage change between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2) and 3 months (T3). The skin area not treated (with cosmetics or placebo) was arbitrarily determined as the control area.

[0163]

[0164] For the treatment with the cosmetic product, a slight but significant increase in skin elasticity was found after 2 and 3 months, equal to 3.7% and 3.8%, respectively. An increase was also found after 1 month; however, this was not significant. No significant increase in skin elasticity was observed in either the placebo group or the control area.

[0165] The results in terms of collagen density are summarized in Tables 3 and Figure 3 The collagen density data are reported as the mean of the values ​​recorded during the test, as the difference and percentage change between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2) and 3 months (T3). The skin area not treated (with cosmetics or placebo) was arbitrarily determined as the control area.

[0166]

[0167] Treatment with the cosmetic product revealed a significant increase in collagen density after 1, 2 and 3 months, equal to 18.4%, 29.1% and 32.4%, respectively. No significant increase in skin elasticity was observed in either the placebo group or the control area.

[0168] Another study was conducted to evaluate the effects of a cosmetic product on collagen density. The cosmetic product was applied in the same manner as those mentioned above, but the treatment was completed over an 8-week period. Figure 4 and Figure 5 Shows a cross-sectional image of the skin of one of the volunteers, processed starting from data collected with the instrument as described above. White areas indicate the presence of collagen.

[0169] Figure 4 Shown are cross sections of the skin area treated with the cosmetic product at the start of the treatment (T0, left) and after 1 month (T1), 2 months (T2) and 3 months (T3) of treatment. Figure 5 Shown instead are skin areas treated with placebo at the start of treatment (T0, left) and after 1 month (T1), 2 months (T2) and 3 months (T3) of treatment.

[0170] In the areas treated with the cosmetic product, there was a visual increase in collagen in the skin at the end of the treatment, whereas no such increase was found in the untreated areas.

[0171] In conclusion, based on the trials reported above, it was found that the application of this cosmetic product over a period of 3 consecutive months allows to significantly increase the water content of the skin by up to 18.9% in the first two months of application, with clearly visible results already obtained after 1 month of application; it allows to slightly but significantly increase the elasticity of the skin by up to 3.7% and 3.8% after 2 and 3 months; and gradually and significantly increase the collagen density by up to 32.4%, with evidence of effectiveness already from the first month of application.

[0172] Obviously, modifications and / or additions may be made to the products and methods described above without departing from the sphere and scope of the invention as defined by the claims.

[0173] It should also be clear that, although the present invention has been described with reference to some specific examples, those skilled in the art will be able to realize other equivalent forms of articles comprising patch products and corresponding production methods, which have the characteristics set forth in the claims and therefore all fall within the scope of protection defined by the claims.

[0174] In the following claims, the only purpose of reference signs in parentheses is to facilitate reading and they shall not be construed as limiting factors with respect to the protective scope defined by the same claim.

Claims

1. A product, comprising a patch product disposed on a base carrier, wherein the patch product comprises a membrane matrix capable of being absorbed by the skin, the membrane matrix being formed by at least one electrospun fiber, the electrospun fiber being composed of a first compound to be electrospun and an electrospinning accelerator, characterized in that: The base carrier comprises a polysaccharide-based biodegradable film that is not absorbable by the skin.

2. The product according to claim 1, characterized in that The non-dermal absorbable film is based on starch, in particular on corn starch.

3. The product according to claim 1 or 2, characterized in that The starch has an amylose concentration greater than 50 wt % based on the weight of the starch.

4. The article according to any one of the preceding claims, characterized in that The film has a thickness of less than 1 mm.

5. The article according to any one of the preceding claims, characterized in that The first compound to be electrospun is selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, albumin, starch, gelatin, collagen, elastin, β-glucan, glycosaminoglycan, mucopolysaccharide, water-soluble polysaccharide and derivatives thereof.

6. The product according to claim 5, characterized in that The electrospinning compound is selected from the group consisting of starch, elastin, hyaluronic acid, heparin, collagen, pectin, β-glucan, chondroitin sulfate, dermatan sulfate, heparan sulfate and derivatives thereof.

7. The article according to any one of the preceding claims, characterized in that The electrospinning accelerator is selected from alginate, pullulan and a mixture thereof.

8. The article according to any one of the preceding claims, characterized in that The membrane matrix also comprises a lipopeptide obtained from a Bacillus species as a surfactant.

9. The product according to claim 8, characterized in that The surfactant is selected from the group consisting of surfactin, pumilacidin and lichenin.

10. The article according to any one of the preceding claims, characterized in that The film matrix also comprises one or more active ingredients selected from peptides and metabolites and derivatives thereof.

11. The product according to claim 10, characterized in that The one or more active ingredients are selected from tetrapeptides, in particular from acetyl tetrapeptides.

12. The product according to claim 11, characterized in that The one or more active ingredients are selected from acetyl tetrapeptide-9, acetyl tetrapeptide-11 and mixtures thereof.

13. A method for producing an article comprising a patch product disposed on a substrate carrier, the method comprising the step of electrospinning a composition comprising a first compound to be electrospun and an electrospinning accelerator to obtain electrospun fibers, wherein the electrospun fibers are directly deposited on the substrate carrier, characterized in that The base carrier comprises a polysaccharide-based film that is not absorbable by the skin.

14. The method according to claim 13, characterized in that The non-dermal absorbable film is based on starch, in particular on corn starch.

15. The method according to claim 14, characterized in that The starch has an amylose concentration greater than 50 wt % based on the weight of the starch.

16. The method according to claim 13, 14 or 15, characterized in that The film has a thickness of less than 1 mm.

17. A primary package comprising a hermetically sealed pouch within which is contained an article according to any one of claims 1 to 12.

18. Primary packaging according to claim 17, characterized in that The pouch is composed of two sheets of heat-sealable material joined to each other by welding.

19. A secondary package comprising a box in which a plurality of primary packages according to claim 17 or 16 are housed.

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